Lab develops cheaper, faster cancer vaccine

Sarah Avery, Duke Medicine News and Communications

In the 20 years since a group of Duke University researchers pioneered the use of RNA-loaded dendritic cells as cancer vaccines, they and many others have shown that this is a safe and effective way to induce tumor-specific immune responses.

Florescence microscopy image of mouse dendritic cells with mRNA-loaded blood cells.

Florescence microscopy image of mouse dendritic cells with mRNA-loaded blood cells.

But the approach has had drawbacks – primarily in the amount of time and money it takes to develop the cells.

Now the researchers, led by Smita K. Nair, Ph.D., associate professor in the Department of Surgery, are moving the science forward with new findings that could significantly improve the utility of this promising therapy.

Appearing in the June 2014, issue of the Journal Advanced Healthcare Materials, Nair and colleagues demonstrate that a tumor vaccine can be formulated by loading RNA into whole blood cells directly after a blood draw without the need for any form of cell culture.

This overcomes the major impediments. The original approach required harvesting cells from the patient via leukapheresis – a step that relies on special equipment and highly trained technicians – to generate dendritic cells from the cellular population. Then the cells were loaded with RNA and injected back into the patient. The process took up to nine days.

Using the new method, the team can create vaccines in less than two hours.

“The therapeutic benefit in mice immunized with mRNA-loaded whole blood cells and those immunized with mRNA-loaded dendritic cells (the gold-standard for cell-based vaccines) was comparable,” Nair said. “This new approach has the potential to be an effective substitute to existing cell-based vaccinations. It could also cut costs for treatment and speed clinical translation of cell-based mRNA tumor vaccines.”

Nair said pre-clinical studies using human blood cells are continuing, with clinical trials on the near horizon.

Duke students present Alzheimer’s research at Montana conference

By Sonal Gagrani

The Federation of American Societies for Experimental Biology (FASEB) brought together neuroimmunologists from all over the world to Big Sky, Montana in July to discuss their current and upcoming research on mechanisms and therapeutics in neuroimmunology.

They covered a plethora of topics in the field from multiple sclerosis, a neurodegenerative brain disorder, to neuroprotection by microglia, the resident immune cells of the brain, to the effects that intestinal imbalances can have on the brain via the blood brain barrier.

My primary focus at the meeting was to expand my knowledge on Alzheimer’s disease (AD), a dementia-causing neurodegenerative disease of the central nervous system that I am currently researching.

photo

Lauren Kane with her poster at the FASEB conference

We were fortunate to have Lauren Kane, a rising senior in Dr. Carol Colton’s lab at Duke and the only undergraduate student with a poster at the conference, be able to present her work on her Alzheimer’s mouse model.

It is known as a CVN-AD model and has many pathologies found in AD such as β-amyloid plaque formation, neuron loss, tau protein defects, and behavioral deficits. Lauren is studying the changes in myelin, the primary make-up of white matter in the brain. Myelin wraps around axons in order to allow faster communication between neurons. She has found that there is some breakdown in myelin in the CVN-AD model, and this could lead us to find treatments for AD that promote remyelination in the brain.

Matthew Kan, an MD/PhD student in Dr. Michael Gunn’s lab at Duke, also presented his work on Alzheimer’s at the conference. He showed in the CVN-AD mouse model that a possible mechanism of neuronal death may be decreased arginine, an essential amino acid in the brain. Microglia produce arginase-1, an enzyme that breaks down arginine, and Matthew found that blocking arginase-1 activity reversed some neurodegeneration found in the CVN-AD mice. This arginine depletion pathway is known to suppress the brain’s immune system rather than cause inflammation, which many people thought was the mechanism for AD pathology in the past. These results may shift some focus to arginine in looking for AD treatments.

The conference strived to integrate and improve neuroimmunology research by providing a venue for creating connections with the experts in the field. There are many therapeutics for brain disorders in progress that key in on the importance of the brain’s immune system in regulating pathology.

Teachers Look to ‘Alice’ for Help

Guest Post by Leah Montgomery, NC Central University

With technology and computer science among the fastest growing fields of study today, it’s a wonder there are so few computer science classes in public middle and high schools.

Florida teacher Chari Distler’s message to a Duke classroom full of her middle and high school teaching colleagues was a promising one: They can get a new generation of kids interested in computer science.

School teachers from all over the country learned programming at Duke this summer.

School teachers from all over the country learned programming at Duke this summer.

All they have to do is follow Alice.

Alice is a 3D virtual worlds programming environment that offers an easy way to create animations for games and storytelling. Since 2008, Duke Professor Susan Rodger has led a two-week summer program training teachers to use Alice to help promote computer literacy among young students.

“What we’re trying to do is teach middle school and high school teachers, in all disciplines, how to program and then help them to integrate it into their discipline,” said Rodger. “The teachers will then expose students to what computer science is. The idea is that if they know what it is then they might choose it as a career when they go to college.”

Distler attended her first Adventures in Alice Programming session at Duke two years ago and returned this week to advise this year’s class on how she implemented the program in her classes.

She said one of her students from North Broward Preparatory School won second place in the annual Alice contest for his animated 45-second video titled “From Rags to Riches.”

Audrey Toney, an instructional coach for teachers in the North Carolina New Schools network, said she learned about Alice through a teacher who wanted to add programming to her curriculum.

“It gives students computational thinking and critical thinking and offers another way to present other than PowerPoint and Prezi,” said Toney.

Toney wants to challenge her professional development students to use Alice to replicate a design of a robotic arm that will lift and unload boxes. The program will allow students to budget money, price the cost of parts and code the robot’s movements.

During the first week of the workshop, teachers get familiar with the Alice software through interactive activities. Teachers created worlds with flying dragons, flipping princesses and annoyed Garfields.

The teachers worked together on learning Alice programming. (Les Todd, Duke Photography)

The teachers worked together on learning Alice programming. (Les Todd, Duke Photography)

In week two, teachers learned about the use of 3-D imaging in the classroom at the Duke Immersive Virtual Environment (DiVE). The teachers also started creating their own Alice-based lesson plans this week. New Jersey high school teacher Kenneth McCarthy said he found his inspiration in the Sunday paper.

“I was thumbing through the Sunday paper and saw Garfield,” said McCarthy, who teaches algebra two and a beginner programming class . “It just looked like something that could be easily used with Alice.”

McCarthy is familiar with Alice, having used the program last year when his students participated in the Hour of Code, an initiative that challenges students and teachers to learn programming in one hour.

“I think the traditional thought was that you have to know algebra two (and other higher mathematics) to learn this, but Alice can be used in elementary schools,” said McCarthy.

Rising Duke senior Samantha Huerta was a workshop assistant for Susan Rodger for nine weeks this summer, helping develop workshop materials and finding ways to integrate computer science into math and other subjects.

“I wasn’t exposed to any type of computer science growing up,” said Huerta. “This is a field that isn’t going to go away, and we need to have more diversity. As a female Latina, I am a double minority and it is my hope to continue researching and bringing diversity to this field.”

A Summer In The Lab, Wounding Flies

By Ashley Mooney

Senior biology major and chemistry minor Rachel Shenker is working as a Dean’s Summer Research Fellow, trying to figure out how certain proteins affect wound-healing in flies.

Rachel Shenker is in Durham this summer, not Sydney.

Rachel Shenker is in Durham this summer, not Sydney.

In particular, she’s working with a protein called integrin, a cell surface signaling protein found in every animal from sponges to humans. Shenker, who is from Rockville Centre, New York, is studying how the protein is involved in fruit fly embryo development and wound healing.

Using fluorescent dyes and a microscope, Shenker is able to see where the protein of interest is in the fly embryos as they develop. She also records images of the embryos for later comparisons.

“What I find really interesting about it is to see how the smallest protein can really change an entire organism,” Shenker said. “Every organism has it in different combinations, so that’s why it’s really relevant to humans and other animals.”

This is the alpha subunit of an integrin receptor. Fruitfly receptors have  5 of these; mammals have 18.

This is the alpha subunit of an integrin receptor. Fruitfly receptors have 5 of these; mammals have 18. (Credit: European Bioinformatics Institute)

Shenker is still trying to understand how integrins function in normal fly embryos, and has not yet started experiments that involve wounding the embryos and observing their reactions. She said once she has a better idea of how the proteins work, she will begin wound-healing experiments.

Shenker conducted similar research in high school and decided to get involved in Biology Professor Daniel Kiehart’s lab after seeing his name in several published papers. She began working in his lab during orientation week of her freshman year, and has been doing research and independent studies ever since. Shenker will use her current research to complete a senior thesis this year.

Beyond her involvement with research, Shenker volunteers at the Duke Cancer Center, is involved with the Jewish Student Union and participates in Greek life. She is also on the executive board of Duke Global Medical Brigades, and has gone on a few trips to Honduras with the program.

“We went to some of the rural areas of Honduras and volunteered in a clinic that we set up to help provide basic healthcare to citizens who really needed it,” she said. “It was a great experience that really put me out of my comfort zone.”

Shenker is currently applying to medical school.

Calderbank Honored For Being Honored

Robert Calderbank

Robert Calderbank (left), shares a laugh with Engineering Dean Tom Katsouleas and Provost Sally Kornbluth at a reception in his honor Wednesday. (Jared Lazarus, Duke Photography)

By Karl Leif Bates

Robert Calderbank, director of the Information Initiative at Duke (iiD) and the Charles S. Sydnor Professor of Computer Science, was the guest of honor at a small reception hosted by top administrators this week.

On July 3, he was named the 2015 recipient of the Claude E. Shannon Award by the IEEE Information Theory Society, the most coveted prize in Calderbank’s field.

“The Shannon Award is as big as it gets in electrical engineering and computer science,” said Tom Katsouleas, dean of the Pratt School of Engineering. “It reflects the fundamental role he’s played in communications, with many of his algorithms in use in mobile phones and internet communications today.”

The iiD is an interdisciplinary program headquartered in Gross Hall, but reaching into many areas of campus, that is increasing Duke’s application of  “big data” computational research.

The Claude Shannon Award honors “consistent and profound contributions to the field of information theory.” It is named for a man considered the father of information theory, who in his 1937 MIT masters thesis first proposed applying Boolean logic to electrical circuits.

Calderbank joined Duke in 2010 to become dean of natural sciences in Trinity College of Arts & Sciences. Previously, he had been directing the Program in Applied and Computational Mathematics at Princeton University since 2004.  Before that, he was vice president for research at AT&T, responsible for one of the first industrial research labs to focus on “big data.”

Calderbank will present a Shannon Lecture at the IEEE International Symposium on Information Theory in Summer 2015 in Hong Kong.

 

Math and Comp Sci Junior Studies Fruit Flies

By Ashley Mooney

dorsal closure

Dorsal closure is a stage in fruitfly embryonic development that is used to study wound-healing.

Roger Zou, a computer science and math major from Solon, Ohio, is working on creating more efficient ways to study wound-healing in fruit flies. It turns out that the way fruit flies heal actually has implications for how mammals heal too.

The junior is developing computational methods that can more accurately quantify cellular properties of fruit flies. As fruit fly embryos develop, he tracks cells through space and time to learn more about a process called dorsal closure. It’s a developmental stage that is similar to wound healing, where a gap in the embryo’s epithelium—which is like its skin—is closed by the coordinated effort of different types of cells. (see movie below)

Roger Zou is a junior spending the summer in Dan Kiehart's lab.

Roger Zou is a junior spending the summer in Dan Kiehart’s lab.

“It’s fun to study the morphological forces because it’s not entirely understood how organisms develop,” Zou said.

In his analysis, Zou uses a laser under a microscope to make cuts on areas of the fly embryos. After making cuts, Zou uses computational methods to measure the wound healing.

Beyond collecting such data, Zou is developing a computer program that analyzes images from the microscope more accurately.

Zou has worked in Biology Professor Daniel Kiehart’s lab since his freshman year. His project was originally a component of a graduate student’s dissertation, but after she graduated, he continued some aspects of her research.

His project has been funded by the Dean’s Summer Research Fellowship for two consecutive summers. He also has done several independent study projects. Although Zou is planning on publishing his research this summer, he will likely use the data eventually to do a senior thesis.

Several of Zou’s math and computer science classes have given him a background in the techniques needed to use a computer to analyze large sets of image data, he said.

“My favorite thing about my research is the ability to learn new things independently,” Zou said. “[Kiehart] is very good at leading me in the right direction but allowing me to be very independent and I think because of that I’ve been able to learn a lot more and learn from my mistakes.”

Outside of his research, Zou is a teaching assistant for the computer science class Data Structures and Algorithms. He also tutors  Duke students in organic chemistry and middle school children in math through the America Reads*America Counts program. And he also does web development for The Chronicle, Duke University’s independent student newspaper.

After graduating, Zou said he hopes to pursue a PhD in either computational biology or computer science or maybe go for a combined MD-PhD program. No matter which program he chooses, Zou said he wants to continue doing research.

Student’s Summer is a Deep Dive into Deep Math

By Ashley Mooney

Math and computer science student Will Victor is spending his summer immersed in Albert Einstein’s theory of general relativity and learning to conduct mathematics research.

Will Victor is a rising senior at Duke who's spending the summer studying math --  for fun!

Will Victor is a rising senior at Duke who’s spending the summer studying math — for fun!

Victor, from Aiken, South Carolina, is working with math and physics Professor Hubert Bray to explore how geometry relates to general relativity. General relativity explains how gravity affects space and time — pulling on them to create curvature we can both predict and measure. Think of how a world map must have curved  latitude and longitude lines so that the representation of distances between spots on the curved surface of the globe are correct.

Victor is studying a class of objects called manifolds. It’s a field of math that describes the surface of complicated structures — anything from landmasses to a misshapen wad of clay — and it has practical applications in areas of mathematical physics such as black holes, dark matter and dark energy, the phenomena that Victor’s mentor studies.

“There’s a lot to be said about how fun it is to really know what the boundaries of the field are and to think about how we might attack answering the questions of what we don’t know,” Victor said.

This summer, he’s reading mathematical research and doing practice problems to learn the material.  “I work problems every day to prepare my mind for research,” Victor said. He also works with Bray’s graduate students to see how they are tackling their own research questions.

The rising senior is part of the PRUV Fellowship program, a 6-week research mentorship sponsored by the Department of Mathematics. After the summer, he will participate in independent studies and eventually write a senior thesis on his research or pursue graduation with distinction.

Victor said his math classes have been essential to preparing him for research by helping him solve math problems, learn theorems, improve proof techniques and get exposure to different types of problems.

“Having a depth and breadth of mathematical knowledge is essential to being able to conduct research in the field,” Victor said. “Learning mathematics consists of acquiring both a formal language and a toolbox of argumentative frameworks which allow a student to speak precisely about theoretical problems.”

Victor noted that the classes he has taken in algebraic structures and classical analysis have provided the framework for talking about any type of modern mathematical question.

Beyond his research, Victor is involved with the selective living group Round Table and a member of the juggling club. He also works with the Community Empowerment Fund, an organization that works with and fosters relationships with the working poor in Durham and Chapel Hill.

“Our goal is to empower people to eventually obtain stable housing and stable employment,” Victor said. “We provide an accountability source for them, so we meet and talk weekly.”

After graduation, Victor says he hopes to go to graduate school in math and continue doing math research. “I enjoy the field I’m in, but I haven’t seen enough math to necessarily know this is what I’m most interested in,” Victor said. “I want to get exposed to more before deciding what I will specialize in.”

Duke Undergrads Sink Their Teeth into Evolution Research

Undergraduates Ben Schwartz (left) and Amalia Cong (center) have spent the past year studying enamel evolution in the labs of Christine Wall (right) and Greg Wray (not pictured).

Undergraduates Ben Schwartz (left) and Amalia Cong (center) have spent the past year studying enamel evolution in the labs of Christine Wall (right) and Greg Wray (not pictured).

By Erin Weeks

The evolution of thick tooth enamel helped turn our species into hard food-chomping omnivores, and two undergraduates are taking a bite out of research to unravel how that happened. Amalia Cong and Ben Schwartz are building on the work of a recent paper that identified precisely where in the human genome natural selection worked to give our species thick tooth enamel. The original study looked only at the potential role of four genes with a known role in tooth development — so now the team is broadening their scope.

“They’re really excited to expand out and push the envelope on new genes,” said Christine Wall, associate research professor of evolutionary anthropology and one of the authors of the paper, along with professor of biology Greg Wray.

Cong and Schwartz arrived in the Wall and Wray labs last summer through a special research session at Duke, the Howard Hughes Vertical Integration Partners (VIP) Program. For ten weeks, they received a crash course in primate evolutionary genomics.

“They had very little time, and the progress they made was astounding,” Wall said. “The success that they had is really a testament to how hard they worked. This has developed into their own research.”

“We’ve begun to expand our tooth enamel gene analysis to include proteins in conjunction with the RNA in order to gain a more holistic understanding of the evolutionary differences that exist between chimpanzees and humans,” Schwartz said. He will continue to work in the lab through this summer, turning the work into a senior thesis.

“One of our goals was to look at the relative expression of these few genes,” Schwartz said, which they’ve done by comparing tooth development in primates of different ages. “Our results correlated very heavily with known functions of these genes in other animals, such as rats.”

The experience has given both students a taste for research, which they hope to continue doing after graduating from Duke. Cong, who hails from a small city outside of Toronto, will be attending dental school in the fall, while Baltimore native Schwartz is interested in pursuing a joint MD/PhD.

Duke Researchers Cited for Their Influence

 

We are the champions, my friend.

We are the champions, my friend.

By Karl Leif Bates

A new compilation of the world’s most-cited scientists just released by Thomson Reuters (our friends from March Madness), shows that 32 Duke researchers are in the top one percent of their fields.

There are 3215 most-cited scientists on the list, so perhaps that makes Duke the one percent of the one percent?

Most-cited means a particular paper has been named frequently in the references by other papers in that field.

And that “is a measure of gross influence that often correlates well with community perceptions of research leaders within a field,” Thomson Reuters says. The database company admits their study methodology does favor senior authors who have had their papers out there longer, but there are quite a few younger Duke researchers in this list too.

From the Medical Center, the tops in citations in clinical medicine are cardiologists  Eric Peterson, Robert Califf, Christopher Granger, and Eric Magnus Ohman. Michael Pencina, a biostatistician at the Duke Clinical Research Institute, is also most-cited in clinical medicine.

Perhaps not surprisingly, Nobel laureate, biochemist, and father of the G-protein coupled receptor Robert Lefkowitz made the list in pharmacology and toxicology.

Barton Haynes and David Montefiori of the Duke Human Vaccine Institute are listed in the microbiology category.

Medical School basic scientist Bryan Cullen of Molecular Genetics and Microbiology was cited in microbiology.

In psychiatry/psychology, A. John Rush, the vice dean for clinical research at Duke-NUS School of Medicine in Singapore, made the list, as did Richard Keefe, Joseph McEvoy of psychiatry and Avshalom Caspi, and Terrie Moffitt of Psychology & Neuroscience in Arts & Sciences.

Also from Trinity College of Arts and Sciences, Ahmad Hariri and HonaLee Harrington of Psychology & Neuroscience also made the list in psychiatry/psychology. Benjamin Wiley was oft-cited in Chemistry, James Berger and Ingrid Daubechies in mathematics, and plant biologists Philip Benfey, Xinnian Dong and Tai-Ping Sun in the category of plant and animal science.

Sanford School of Public Policy Dean Kelly Brownell is on the list in general social sciences, along with Arts & Sciences sociologist James Moody and nutrition researcher Mary Story of community and family medicine and the Duke Global Health Institute.

Nicholas School of the Environment researchers Robert Jackson and Heather Stapleton were cited the environment/ecology category.

From the Pratt School of Engineering, David R. Smith was cited in the physics category and Jennifer West in materials science.

The economics and business category includes Dan Ariely along with his Fuqua School of Business colleagues Campbell Harvey and Arts & Sciences economist Tim Bollerslev.

The Thomson Reuters analysis is based on their Web of Science database. This is the first time it has been done since 2001, when there were 45 Duke names on the list (including five that appeared again this time), but the methodology has changed somewhat.

UPDATE – There’s now a full PDF report  from Thomson Reuters for download - http://sciencewatch.com/sites/sw/files/sw-article/media/worlds-most-influential-scientific-minds-2014.pdf